Dosing system for a nebulizer

ABSTRACT

The invention provides a dosing system for an inhalation device, comprising a filling chamber (10); a reservoir chamber (31) which supplies liquid (3) to an aerosol generator (301); and a plunger (20) which includes an overflow chamber (25) and which is pivotable about a hinge (50). The filling chamber has an inner wall (12) which is higher on the side adjacent to the hinge than on the opposite side. When the filling chamber is filled with liquid and the plunger is pivoted into the filling chamber, part of the liquid is displaced over the lower side (17) of the inner wall into the reservoir chamber and some or all of the remaining liquid is displaced into the overflow chamber. The invention also provides an inhalation device comprising the dosing system and a method for dosing liquid to the inhalation device.

Nebulizers are inhalation devices that convert a liquid formulation,which usually contains an active agent, into an inhalable aerosol (i.e.a dispersion of fine liquid droplets), for example by means of anultrasonic aerosol generator, a jet or a vibrating mesh. The aerosol isdelivered to the lungs by inhalation, particularly for the treatment ofrespiratory diseases such as asthma and cystic fibrosis.

Nebulizers differ from other inhalation devices such as dry powderinhalers, pressurized metered dose inhalers and soft mist inhalers inthat they operate continuously. Treatment may take place during a fewbreaths or for an extended period of time (e.g. up to about 45 minutes).During this time, the nebulizer emits aerosol either constantly or inpulses which may be adapted to the user's breathing pattern; forexample, aerosol generation may be triggered by the onset of inhalation.Thus, nebulizers do not per se emit metered amounts of aerosols, andunless switched off, they produce aerosol until the liquid has all beenused up.

Consequently, it is necessary to dose the correct amount of liquidformulation to the aerosol generator. One way of doing this is to usepre-filled single-use cartridges which are completely emptied into thenebulizer, so that the liquid is all nebulized. However, the dosingflexibility of such cartridges is limited because a particular cartridgecan only dose one fixed volume. Thus when the prescribed amount ofmedicine to be inhaled does not match the volume of the liquid suppliedin the container, it is necessary to ensure that only the prescribedamount is delivered in aerosol form.

BACKGROUND TO THE INVENTION

A dosing system for this purpose is disclosed in EP 1 465 692, having ametering chamber and a second (overflow) chamber. The metering chamberdefines the volume of the substance to be nebulized and is arranged soas to feed this volume to the aerosol generator, while any substancepoured into the metering chamber in excess of its volume is received andretained in the second chamber. In other words, the metering chamber isfilled until the liquid overflows into the second chamber, and only themetered volume inside the metering chamber is subsequently nebulized.This has the disadvantage that any changes in the prescribed dose wouldrequire complete replacement of the metering chamber assembly.Furthermore, the metering system is not suitable for metering very smallamounts of liquids which are substantially affected by adhesive andcohesive forces and do not easily flow from one chamber to another.

Further dosing systems are disclosed in EP 1 205 199 and EP 2 496 293.Both of these have a filling chamber with a wider upper portion and anarrower lower portion that is closed by a valve at its bottom end. Aplunger is inserted into the filling chamber from its wider upper endalong the chamber's longitudinal axis. Once the plunger reaches thenarrower lower portion, a seal is formed between the plunger and thewalls of the lower portion, so that liquid can no longer be displacedupwards into the upper portion. Upon continued insertion of the plunger,the liquid in the lower portion is pushed out through the valve, thusdosing a metered volume, while the excess liquid remains in the upperportion above the seal. The dispensed volume can be altered by changingthe volume and/or the extent of insertion of the plunger. The plungeractively displaces the liquid to be dosed, thus overcoming the issuesassociated with dispensing small amounts of viscous liquids. When theplunger is retracted, the excess liquid can flow into the lower portionand could be pushed out through the valve if the plunger is re-inserted.This is advantageous when the filling chamber is deliberately filledwith a multi-dose amount of liquid and the dosing system is supposed tobe actuated repeatedly. However, it is highly undesirable in cases wheresuch re-dosing is unintended and may even be harmful due to overdosing.For example, only small amounts (substantially less than the suppliedvolume) of liquid formulation may be intended to be administered toneonates, infants, or children, or to subjects with an improvinghealth-condition. For instance, the liquid formulation may only beavailable in ampoules containing 1 mL or more, while the subject shouldreceive only 200 μL. The dosing systems of EP 1 205 199 and EP 2 496 293would allow the unintended administration of an extra 800 μL to thepatient.

WO 2015/022436 discloses a dosing system having both an overflow chamberand a plunger which forms a seal with the filling chamber, in order toisolate the excess volume of liquid that is not supposed to beadministered to the user, so that it cannot be re-dosed accidentally.Two general types of dosing system are disclosed. In the first, thefilling chamber is separated from the aerosol generator chamber by aclosing means, such as a duckbill valve. Liquid is poured into thefilling chamber, where it is retained by the valve. The plunger isinserted, thereby displacing some of the liquid into the overflowchamber. The plunger must then form a seal with the filling chamberwall, so that it can apply pressure to the liquid in order to open thevalve and supply a metered volume of liquid to the aerosol generatorchamber. In the second type of dosing system, there is no valve betweenthe filling chamber and aerosol generator; nonetheless a seal betweenthe plunger and the filling chamber is necessary, in order to isolate ametered volume of liquid. However, the requirement of forming a sealmeans imposes requirements on the materials from which the plungerand/or filling chamber are made, and/or require additional components,such as O rings.

When the user opens the lid of the dosing system (as in EP 1 465 692)and/or removes the plunger (as in EP 1 205 199, EP 2 496 293 and most ofthe embodiments of WO 2015/022436) after nebulization, the excess liquidis visible to the user. As a result, the user may mistakenly think thatthey have not received the full dose, and thus may try to use theexcess, which could result in an overdose. Alternatively, the user mightunderstand that they have received the correct dose, but then try to usethe excess liquid for a subsequent dose, in order not to waste theliquid, which could result in the incorrect dose and also lead tocontamination.

Thus there is a need for an improved dosing system which can accuratelydispense pre-determined volumes of liquid, especially small amounts,which does not suffer from the drawbacks of the previous dosing systems.

BRIEF DESCRIPTION OF THE INVENTION

In a first aspect, the present invention provides a dosing system for aninhalation device, comprising:

-   -   (a) a filling chamber for receiving a liquid to be aerosolized,        the filling chamber having an outer wall, a base and an inner        wall which defines an outlet opening,    -   (b) a reservoir chamber for supplying liquid an aerosol        generator,    -   (c) a plunger which is mounted on a hinge and which includes an        overflow chamber,        wherein the inner wall of the filling chamber is higher on the        side adjacent to the hinge than on the opposite side so that        when the filling chamber is filled with liquid and the plunger        is inserted into the filling chamber by pivoting it about the        hinge, part of the liquid is displaced by the plunger over the        lower side of the inner wall of the filling chamber and into the        reservoir chamber via the outlet opening, and some or all of the        remaining liquid is displaced by the plunger from the filling        chamber into the overflow chamber.

Preferably the dosing system comprises a cap located above the fillingchamber outlet opening which prevents liquid from being supplieddirectly into the reservoir chamber.

Preferably the plunger has an inner wall and an outer wall, and at leastpart of the inner and outer walls of the filling chamber and the plungerare curved in profile so that there is a close fit between the innerwalls of the plunger and filling chamber when the plunger is fullyinserted into the filling chamber.

Preferably the hinge is provided with a detent mechanism which resiststhe pivoting motion of the plunger in order to prevent the plunger frombeing inserted rapidly, which could cause some of the liquid to splashout of the filling chamber.

Preferably the top of the lower side of the inner wall of the fillingchamber and the top of the inner wall of the plunger are at the sameheight when the plunger is fully inserted.

Preferably a partition is located inside the inner wall of the fillingchamber, which more preferably is parallel to the hinge and even morepreferably extends vertically down into the reservoir chamber. Theliquid which is displaced from the filling chamber when the plunger isinserted flows over the lower part of the inner wall and down thecorresponding side of the reservoir chamber. The higher part of theinner wall prevents liquid from flowing down on the opposite side, sothat air is displaced upwardly on that side of the reservoir chamber.This prevents the formation of an airlock, i.e. a trapped bubble of airat the bottom of the reservoir chamber.

Conveniently, the cap can be formed as an extension of the partition.

Preferably the overflow chamber has a cover on the side adjacent to thehinge, which closes the top of the overflow chamber on this side. Morepreferably the cover comprises a semi-annular wall and a semi-annularfloor which preferably slopes slightly downwards from the outer wall ofthe overflow chamber adjacent to the hinge towards the opposite side ofthe overflow chamber (when the plunger is inserted). Thus, as theplunger is inserted, excess liquid is displaced over the lower side ofthe filling chamber inner wall and enters the uncovered part of theoverflow chamber. The higher part of the filling chamber inner wall,together with the cover wall prevents liquid from flowing onto the topof the cover floor, or at least minimizes the amount of liquid thatflows on to the top of the cover floor. Nonetheless, the slope of thecover floor guides any liquid which passes over or round the higher partof the filling chamber inner wall, or over the filling chamber outerwall, back down the slope towards the uncovered part of the over flowchamber opening and into the overflow chamber. Moreover, when theplunger is opened after nebulization has been completed, the cover flooris in a generally vertical orientation. In this position, the coverprevents liquid from flowing out of the overflow chamber. The covercloses enough of the top of the overflow chamber so that the liquidcannot flow out when the plunger is pivoted into the open position.

Preferably the plunger has a lid which covers the top of, and preventsdirect access to, the overflow chamber, so that liquid cannot be filleddirectly into the overflow chamber, and so that the excess liquid is notvisible to the user after nebulization. The lid is preferably fixed sothat it is difficult for the user to access the overflow chamber. Inorder to allow the overflow chamber to be emptied and cleaned afternebulization has been completed, there is preferably an opening betweenthe lid and the top of the overflow chamber. Preferably the opening isformed without a spout or other means of facilitating pouring out of theliquid, so that it is possible, but somewhat awkward, for the user toempty the overflow chamber. This emphasizes to the user that the excessliquid is not intended to be re-used.

Alternatively, the lid may be removable or openable, which facilitatesemptying and cleaning of the overflow chamber after use. For example,the overflow chamber may be separately pivotable. Preferably theoverflow chamber and lid have clip formations so that when the lid isclosed, it becomes attached to the overflow chamber.

Preferably the overflow chamber corresponds to the size and shape of thefilling chamber, so that the plunger forms a close fit and preferablyoccupies substantially the whole of the filling chamber when inserted.Nonetheless, when the filling chamber has an inner wall, there ispreferably a small gap between the inner wall of the filling chamber andplunger (when inserted), through which the liquid displaced from thefilling chamber flows. Preferably the gap is from 0.1 to 0.2 mm inwidth, such as about 0.15 mm.

Preferably the filling chamber and overflow chamber are generallyannular in shape. Preferably the plunger is shaped so that it cannot beinserted into the reservoir chamber.

Preferably the filling chamber and the plunger are made from a rigidmaterial, such as a rigid plastic.

In a second aspect, the present invention provides an inhalation devicecomprising the dosing system of the first aspect of the invention.

Preferably the inhalation device comprises an aerosol head and a baseunit which are detachably connectible with each other, and wherein theaerosol head comprises the dosing system. More preferably, the aerosolhead and base unit have complementary male and female features whichinterlock to provide a recognition system, for example, the base unithas two pegs of different sizes and the aerosol head has twocorresponding holes.

In a third aspect, the present invention provides a method for dosingliquid to an inhalation device according to the second aspect of theinvention, the method comprising supplying a liquid to be aerosolized tothe filling chamber; and inserting the plunger into the filling chamberso that part of the liquid is displaced over the lower side of the innerwall of the filling chamber and into the reservoir chamber, and some orall of the remaining liquid is displaced into the overflow chamber.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is further described with reference to thedrawings, in which:

FIGS. 1, 2, 3 and 4 illustrate the general principle of a dosing system

FIG. 5 shows side views of a dosing system according to the inventionbefore and after the plunger is inserted into the filling chamber

FIG. 6 shows cross-sectional views which correspond to the side views ofFIG. 5

FIG. 7 shows a front view of the dosing system of FIG. 5 before theplunger is inserted into the filling chamber

FIG. 8 shows a corresponding view of the dosing system of FIG. 5 fromabove

FIG. 9 is an expanded view showing the components of the dosing systemof FIG. 5

FIG. 10 shows the operation of the dosing system of FIG. 5

FIG. 11 shows a nebulizer device

FIG. 12 shows the aerosol generator of the nebulizer device of FIG. 11

FIG. 13 shows a recognition system for the nebulizer device of FIG. 11

LIST OF NUMERICAL REFERENCES USED IN THE FIGURES

1 Dosing system 3 Liquid 10 Filling chamber 11 Filling chamber outerwall 12 Filling chamber inner wall 13 Filling chamber base 14 Fillingchamber outlet opening 15 Central space 16 Higher side of inner wall 17Lower side of inner wall 20 Plunger 21 Plunger outer wall 22 Plungerinner wall 23 Plunger base 25 Overflow chamber 26 Gap 27 Lid 28 Overflowchamber outlet opening 31 Reservoir chamber 34 Perforated membrane 35Partition 37 Cap 50 Hinge 51 Curved region of filling chamber inner wall52 Curved region of plunger inner wall 53 Straight region of fillingchamber inner wall 54 Straight region of plunger inner wall 55 Cut-awayregion 56 Curved region of filling chamber outer wall 57 Curved regionof plunger outer wall 61 Cover 62 Cover floor 63 Cover wall 64 Uncoveredregion of overflow chamber 100 Base unit 102 Air outlet opening 103Groove 104 Base unit key lock members 106 Indentation 140 Pegs 200Mouthpiece 201 Air inlet opening 202 Lateral opening 203 Aerosol outletopening 204 Positioning member 300 Aerosol head 301 Aerosol generator303 Aerosol head key lock members 306 Transducer body 308 Piezoelectricmember 310 Filling chamber 328 Screw thread 331 Reservoir 334 Perforatedmembrane 340 Holes

FIGS. 1 to 4 (not according to the invention) illustrate the generalprinciple of a dosing system. The dosing system 1 has a filling chamber10 for receiving the liquid 3 to be nebulized. The filling chamber hasan outer wall 11, an inner wall 12 and a base 13, and is open at itsupper end.

The outer and inner walls are circular (when viewed from above), so thatthe filling chamber 10 is annular. The top of the inner wall 12 forms anoutlet opening 14. The inner wall 12 also defines a central space 15which lies inside it. Situated beneath the central space 15 is areservoir chamber 31 which supplies liquid to an aerosol generator. Theinner wall 12 therefore acts as a barrier which prevents liquid fromflowing from the filling chamber to the reservoir chamber.

The aerosol generator may be, for example, a vibrating perforatedmembrane 34. The membrane 34 has a large number of holes, typically fromabout 1 μm to about 10 μm in diameter at the exit (aerosol) side of themembrane. Without vibration of the membrane, the balance of pressures,the shape of the holes and the nature of the material used for themembrane are such that the liquid does not seep out through themembrane. However, vibration of the membrane leads to the formation andemission of aerosol droplets through the holes.

The dosing system has a plunger 20 for insertion into the fillingchamber. The plunger has an outer wall 21, an inner wall 22 and a base23 which connects the outer and inner walls. Together, the walls andbase form an overflow chamber 25. In contrast to some of the dosingsystems of WO 2015/022436, the plunger is not (and cannot be) insertedinto the reservoir chamber. This is advantageous because there is norisk of the plunger being forced too far into the reservoir chamber andcoming in to contact with the membrane 34.

The plunger is also annular (when viewed from above) and corresponds tothe size and shape of the filling chamber, so that they form a close fitwhen the plunger is inserted. Nonetheless, there is a small gap 26between inner walls 12, 22 of the filling chamber and plunger throughwhich the liquid displaced from the filling chamber flows. The gap maybe from 0.1 to 0.2 mm in size, such as about 0.15 mm. The top of theinner wall 12 of the filling chamber and the top of the inner wall 22 ofthe plunger 20 are at the same height when the plunger is fullyinserted, as shown in FIG. 3.

The plunger has a lid 27 which covers the top of the overflow chamber25. The lid hides the excess liquid from the user after nebulization. Incontrast, in the known dosing systems described above, the excess liquidis visible to the user once the plunger is been removed afternebulization. The presence of visible liquid may confuse the user, whomay think that this liquid should have been nebulized, and who thereforemay be tempted to try to pour the excess liquid back into the fillingchamber, and hence dose more than the correct amount.

The dosing system operates as follows. The liquid 3 is poured into thefilling chamber 10, for example from a cartridge or ampoule (FIG. 1).The inner wall 12 prevents liquid from flowing directly into thereservoir chamber 31. When the plunger 20 is inserted (FIG. 2), some ofthe liquid in the filling chamber 10 is displaced through the gap 26between the inner walls of the filling chamber and plunger, over thefilling chamber inner wall 12, through the outlet opening 14 and intothe reservoir chamber 31. Once the reservoir chamber 31 and the centralspace 15 inside the inner wall 12 of the filling chamber is full ofliquid (3 a, 3 b respectively), the remaining liquid in the fillingchamber 10 is displaced over the inner wall 22 of the plunger 20 andinto the overflow chamber 25. Once the plunger has been fully inserted(FIG. 3), if a small residual amount of liquid (e.g. the liquid from thegap 26) remains in the filling chamber, it is prevented by the innerwall 12 from entering the reservoir chamber 31 and therefore beinginadvertently nebulized. The liquid 3 a in the reservoir chamber 31together with the liquid 3 b in the central space 15 is available to benebulized.

The excess liquid 3 c is isolated and retained in the overflow chamber25, and cannot be nebulized. The dosing system thus dispenses a meteredvolume of liquid (3 a+3 b) to the aerosol generator.

After nebulization has been completed, the excess liquid is poured outof the overflow chamber. The dosing system can then be rinsed out beforethe next use. The plunger, filling chamber or the whole dosing systemmay be removable from the nebulizer device so that it can be cleaned bythe user, for example rinsed with water and/or placed into a dishwasher.

In FIGS. 1 to 3, the plunger 20 occupies essentially the whole of thefilling chamber 10 when fully inserted (apart from the gap 26), so thatlittle or no residual liquid remains in the filling chamber. In avariant shown in FIG. 4, the plunger 20 occupies less than the wholevolume of the filling chamber 10 when fully inserted so that a portionof the excess liquid 3 c is displaced into the overflow chamber, whilstanother residual portion 3 d remains in the filling chamber. Thisresidual liquid 3 d is prevented by the inner wall 12 from entering thereservoir chamber 31 during nebulization. However, this is lesspreferred, as after nebulization has been completed, the user may seethe liquid 3 d remaining in the filling chamber and think that it shouldhave been nebulized.

In the schematic views of FIGS. 1 to 4, the plunger is shown as beinginserted linearly downwards into the filling chamber for simplicity.However, in the dosing system of the invention, shown in FIGS. 5 to 9,the plunger is inserted and removed by a pivoting motion about a hinge50. This results in the plunger being inserted at a slight angle.Consequently, parts of the walls of the plunger and filling chamber areshaped as appropriate matching curves. The connection between theplunger and the hinge may be designed to allow an easy exchange of theplunger, while at the same time preventing accidental loss of theplunger.

FIGS. 5A and 5B show side views before and after the plunger 20 isinserted into the filling chamber 10 respectively. FIGS. 6A and 6B showthe corresponding cross-sectional views. FIGS. 7 and 8 are views of thedosing system in the open position (i.e. before insertion of theplunger) from the front and from above respectively. FIG. 9 is anexpanded view showing the components of the dosing system.

As can be seen in FIG. 6B, the inner walls of the filling chamber andthe plunger are curved 51, 52 in the region close to the hinge 50, sothat the plunger can be pivoted into the filling chamber whilst alsoensuring a close fit between the inner walls when the plunger is fullyinserted. Nonetheless, the plunger does not need to form apressure-tight seal with the filling chamber, and indeed intentionallydoes not do so, in order to provide a gap through which the liquiddisplaced from the filling chamber can flow.

Moreover, since there is no need for a seal, unlike the dosing systemsof WO 2015/022436, the plunger and/or filling chamber do not need to bemade from flexible materials, nor are additional components, such as Orings, required. Thus the construction of the dosing system issimplified. Conveniently therefore, the plunger and filling chamber aremade from a rigid material, preferably a rigid plastic material.

As a result of the curvature, the bottom of the curved part 51 of theinner wall of the filling chamber meets the outer wall 11 on the sideclosest to the hinge (shown in FIG. 6A), so that it also effectivelyforms the base 13 a of the filling chamber in this region.Correspondingly, the bottom of the curved part 52 of the inner wall ofthe plunger also meets the outer wall 21 on the side closest to thehinge and forms the base of the plunger 23 a in this region. Thus thecurved part of the inner wall of the plunger 52 forms a cut-away region55 in the annular shape of the plunger, as shown in FIG. 7. In contrast,the inner walls of the filling chamber and the plunger are notconstrained by the pivoting motion on the side opposite the hinge 53,54, and therefore can be straight.

The outer wall 11 of the filling chamber and the outer wall 21 of theplunger are curved in their respective regions 56, 57 where they arefurthest from the hinge 50 for the same reasons. Since they are furtherfrom the hinge, the radius of curvature is greater for the curvedregions 56, 57 of the outer walls than for the curved regions 51, 52 ofthe inner walls. Although not necessary for the pivoting motion, theouter walls may have the same curvature everywhere for simplicity andaesthetic appearance. Thus, as shown in FIG. 9, the outer walls 11, 21of the filling chamber and plunger are both curved, with a smallincrease in diameter from the base to the top as a result of theshaping.

Inserting the plunger too rapidly could cause liquid to splash out ofthe filling chamber, rather than steadily displacing it into thereservoir chamber and overflow chamber. In order to prevent this, thehinge may be provided with a detent mechanism which resists the pivotingmotion of the plunger. The detent mechanism may operate over the wholepivoting motion, or only in the latter part, i.e. as the plunger comesinto contact with the liquid in the filling chamber. The detentmechanism may be any mechanism which is capable of applying a biasingforce to the plunger, e.g. a spring or a cam follower associated withthe plunger and a corresponding track associated with the fillingchamber.

Due to the pivoting motion, the overflow chamber is rotated throughapproximately 90 degrees when the plunger is moved back into the openposition after nebulization. In order to prevent the excess liquid fromflowing out of the overflow chamber in this position, there is a cover61 between the inner 22 and outer 21 walls on the side adjacent to thehinge, visible in FIGS. 6 and 9. The cover comprises a semi-annularfloor 62 and a corresponding semi-annular wall 63.

When the overflow chamber 25 is in the open position (FIG. 6A), thecover floor 62 is in a generally vertical orientation. The cover floormust close enough of the overflow chamber so that the liquid cannot flowout when the plunger is pivoted into the open position. For example, asis apparent from FIG. 9, the cover 61 suitably closes the top of theoverflow chamber 25 on the side adjacent to the hinge 50 to preventliquid from flowing out of the overflow chamber, whereas the other side64 is uncovered.

The filling chamber inner wall is higher 16 on the side adjacent to thehinge than on the opposite side 17 (see FIGS. 6 and 9). Thus when theplunger is inserted, excess liquid is displaced over the lower side 17of the filling chamber inner wall and enters the open (uncovered) region64 of the overflow chamber on the side opposite the hinge. Liquid mayalso be displaced upwards between the filling chamber outer wall and theoverflow chamber outer wall. In order to ensure that this liquid doesnot seep out of the dosing system, the filling chamber outer wall 11 ishigher than the overflow chamber outer wall 21, as shown in FIG. 6B.

The higher part 16 of the filling chamber inner wall, together with thecover wall 63 prevents liquid from flowing onto the top of the coverfloor 62, or at least minimizes the amount of liquid that does so.Nonetheless, the cover floor 62 is not exactly horizontal (in the closedposition) but instead slopes downwardly away from the hinge 50.Consequently any liquid which passes over or round the higher part ofthe filling chamber inner wall, or over the filling chamber outer wall,and onto the top of the cover floor 62, is guided back down the slopetowards the open (uncovered) region 64 and into the overflow chamber 25.

The plunger 20 has a fixed lid 27 which covers the top of the overflowchamber 25, so that the user cannot put the liquid directly into theoverflow chamber by mistake. The plunger has an overflow chamber outletopening 28, shown in FIG. 5, which extends around the wholecircumference of the outer wall without a spout. The outlet opening 28makes it possible, but somewhat awkward, for the user to pour the excessliquid out of the overflow chamber after nebulization has beencompleted, in order to emphasize that the excess liquid is not intendedto be re-used.

Alternatively, the lid may be separable from the overflow chamber inorder to facilitate emptying and cleaning of the overflow chamber afteruse. For example, the lid and overflow chamber may be separatelypivotable. The overflow chamber and lid may have clip formations so thatwhen the lid is closed, it becomes attached to the overflow chamber.Thus, after nebulization has been completed, the lid and overflowchamber are pivoted together, and the excess liquid in the overflowchamber is not visible to the user. When the plunger is in the openposition, the clip formations can be detached from each other, so thatthe user can then open the lid, in order to pour out the excess liquidand clean the overflow chamber. The action of having to unclip the lidbefore pouring out the excess liquid acts as a reminder to the user thatthe excess liquid is not intended to be re-used.

The whole dosing system can be removed from the nebulizer so that thefilling chamber, overflow chamber and reservoir chamber can be cleanedby the user, for example rinsed with water and/or placed into adishwasher.

As shown in FIGS. 6 and 9, the central space 15 inside the inner wall ofthe filling chamber is divided by a partition 35 which is parallel tothe hinge and extends vertically down into the reservoir chamber 31,thereby separating the central space 15 and reservoir chamber 31 intotwo parts (15 a, 31 a and 15 b, 31 b respectively). The partitionhowever does not extend all the way to the membrane 34, so that thereservoir chamber is not divided at the bottom. Since the inner wall ofthe filling chamber is higher 16 on one side of the partition, and lower17 on the other, the liquid which is displaced from the filling chamber10 when the plunger 20 is inserted flows over the lower part 17 of theinner wall and down the corresponding side of the central space 15 a andreservoir chamber 31 a to the bottom of the reservoir chamber 31. At thesame time, air is displaced upwards on the other side of the reservoirchamber 31 b and the central space 15 b, and over the higher part 16 ofthe inner wall. This prevents the formation of an airlock, i.e. atrapped bubble of air at the bottom of the reservoir chamber.

The partition 35 occupies part of the volume defined by the reservoirchamber 31 and the central space 15, and thus reduces the free volumewhich can be occupied by the liquid. The volume of liquid dispensed isgiven by the volume of the reservoir chamber plus the volume of thecentral space up to the lower part of the filling chamber wall minus thevolume of these which is occupied by the partition. The partitiontherefore provides a further advantage, namely the ability to dispensesmaller volumes of liquid than would otherwise be possible. Thethickness and or length of the partition can be chosen according to thedesired volume of liquid to be nebulized.

The central space 15 inside the filling chamber inner wall 12 may becovered with a cap 37 (see FIGS. 6, 8 and 9). This prevents the userfrom dosing liquid directly into the reservoir chamber 31 whilstallowing liquid to be dosed into the filling chamber. Consequently (andunlike those dosing systems of WO 2015/022436 in which there is a fixedbarrier between the filling chamber and the reservoir chamber), there isno need for a mechanism (such as a safety plunger) to prevent accidentaloverfilling of the reservoir chamber. Conveniently, the cap 37 can beformed as an extension of the partition 35.

FIG. 10 shows the dosing system of FIGS. 5 to 9 in operation. In FIG.10A, the plunger 20 is in the open position and the filling chamber 10contains liquid 3. In FIG. 10B, the plunger 20 has been partly closedand partially inserted into the filling chamber 10, so that it hasdisplaced some of the liquid 3 over the lower side of the inner wall 17and into the central space 15 a, from where it flows down into thereservoir chamber 31 a. Air is displaced up the other side 31 b, 15 b.As the plunger is pivoted further into the filling chamber, the centralspace and reservoir chamber are filled with liquid 3 j, shown in FIG.10C. Thereafter, the remaining (i.e. excess) liquid 3 k is displacedfrom the filling chamber over the plunger inner wall 22 and into theoverflow chamber 25 until the plunger has been completely inserted,shown in FIG. 10D.

The dosing system is suitable for use with the nebulizer device shown inFIG. 11, which is described in detail in EP 2 724 741. The devicecomprises three parts: a base unit, a mouthpiece, and an aerosol head.The base unit 100 has one or more air inlet opening(s), an air outletopening 102, a groove 103 for receiving the mouthpiece 200, and one ormore key lock members 104. The mouthpiece 200 has an air inlet opening201 which is attachable to the air outlet opening 102 of the base unit100, a lateral opening 202 for receiving an aerosol generator 301, andan aerosol outlet opening 203. The mouthpiece 200 is insertable into thegroove 103 of the base unit 100. The aerosol head 300 has an aerosolgenerator 301 and one or more key lock members 303 complementary to thekey lock members 104 of the base unit 100. In FIG. 11, the dosing systemis not shown, but may be attached to the aerosol head 300 by means of ascrew thread 328.

The base unit 100, the mouthpiece 200 and the aerosol head 300 aredetachably connectible with one another. The device is assembled byinserting the mouthpiece 200 into the groove 103 in the base unit 100,then placing the aerosol head 300 over the mouthpiece 200 and engagingthe key lock member(s) 303 of the aerosol head 300 with thecomplementary member(s) 104 of the base unit 100 by gentle pressure onboth the aerosol head and the base unit. The aerosol generator 301 ispositioned in the aerosol head 300 in such a way that when engaging thekey lock member(s), the aerosol generator 301 is inserted into thelateral opening 202 of the mouthpiece 200. This creates airtightconnections between the aerosol generator 301 and the lateral opening202 in the mouthpiece as well as between the air outlet opening 102 ofthe base unit 100 and the air inlet opening 201 of the mouthpiece 200.The base unit 100, the mouthpiece 200 and the aerosol head 300 can beseparated by reversing these steps.

The base unit 100 may have one or more indentation(s) 106 whose positionmay be at or near the groove 103, and the mouthpiece 200 may have one ormore positioning member(s) 204. The indentation(s) of the base unit arecomplementary to (i.e. shaped to receive) the positioning member (s) 204of the mouthpiece 200. In this context, an indentation is a depression(e.g. a recess, pit, cavity, void, notch or the like) whose “negative”shape is complementary to the “positive” shape of a positioning member(which may be a flange, projection, nose, bulge or the like). Together,such indentations and positioning members act to position the mouthpiececorrectly in the base unit. The indentation(s) 106 and the positioningmember(s) 204 may be asymmetrical, so as to ensure that the mouthpiece200 can only be inserted into the indentation 106 of the base unit 100in one particular manner. This ensures that the device is assembled insuch a way that the position and orientation of the mouthpiece 200 andbase unit 100 relative to each other are correct.

The aerosol generator 301 is preferably an ultrasonic liquid atomisercomprising a piezoelectric member 308 and a transducer body 306 as shownin FIG. 12 and described in WO 2008/058941. The transducer body 306 ismade of e.g. stainless steel, titanium or aluminium, and encloses thereservoir chamber 331. The reservoir chamber 331 is connected to thedosing system (not shown in FIG. 12) so as to receive liquid to benebulized from it.

The piezoelectric member 308 is preferably an annular single ormultilayer ceramic, which vibrates the transducer body 306 in alongitudinal mode, at a frequency preferably in the 50 to 200 kHz range.As a result, micronic longitudinal displacements, or deformations, occurin a direction parallel to the symmetry axis of the transducer body 306.The transducer body 306 has a region close to the piezoelectric member308 with a relatively large wall thickness, which serves as a stressconcentration zone 306 c, and a region downstream thereof 306 d with arelatively low wall thickness which serves as a deformationamplification zone. In this configuration, the vibrations ordeformations of the transducer body 306 caused by the piezoelectricmember 308 are amplified. Preferably, the piezoelectric member 308 islocated at the level of, or adjacent to, the stress concentration zone306 c. The internal diameter of the transducer body 306 at thedeformation amplification zone 306 d may be the same as at the stressconcentration zone 306 c, so that the differences in wall thicknesscorrespond to different external diameters. Alternatively, the externaldiameter of the transducer body 306 may be constant, while the innerdiameters differ at the position of the two zones.

A perforated membrane 334 is positioned at the downstream end 306 b ofthe transducer body 306. The holes may be formed by electroforming or bylaser drilling, with openings normally being in the range from about 1μm to about 10 μm. Without vibration of the membrane, the balance ofpressures, the shape of the holes and the nature of the material usedfor the membrane are such that the liquid does not seep out through themembrane. However, vibration of the membrane leads to the formation andemission of aerosol droplets through the holes. The membrane may be madeof plastic, silicon, ceramic or more preferably metal, and may beaffixed to the downstream end 306 b of the aerosol generator 301 byvarious means, such as gluing, brazing, crimping or laser welding.Optionally, the membrane at least partially forms a dome in its centralregion, which causes the jet of nascent aerosol droplets to diverge andhence reduces the risk of droplet coalescence.

Once a treatment operation has been completed, the aerosol head key lockmembers 303 are disengaged from the complementary member(s) 104 of thebase unit, so that the aerosol generator 301 can be removed from thelateral opening 202 of the mouthpiece.

A patient may receive two (or more) different drugs, which willgenerally require different volumes of liquid to be dispensed, anddifferent aerosolisation parameters, such as droplet size, treatmenttime etc. Thus a patient may have two (or more) different nebulizationdevices which are adapted for the different drugs. The first aerosolhead has a dosing system designed to dispense the appropriate volume ofliquid and the first base unit is configured to provide the appropriateaerosolisation parameters for the first drug. Similarly the secondaerosol head and base unit are configured to dispense and aerosolize thesecond drug. A recognition system can be provided to ensure that thepatient uses the correct combinations of aerosol head and base unit. Therecognition system could be, for example, based on RFID tags, electricalcontacts or mechanical interlock.

A simple mechanical recognition system consists of complementary maleand female features on the aerosol head and base unit, for example, oneor more cavities/holes on the aerosol head and correspondingprotrusions/pegs on the base unit. These may be present in one or morelocations and/or sizes and/or shapes selected from a pre-determinednumber of locations and/or sizes and/or shapes. Conveniently, thecomplementary features can be located on or formed as part of the keylock members 104, 303. Alternatively the complementary features may beon other parts of the aerosol head and base unit.

FIG. 13 shows an example of a recognition system which has several (e.g.five) potential hole locations on the aerosol head 300 and correspondingpotential peg locations on the base unit 100. Each hole and peg can beeither large or small, in order to maximise the number of possiblevariants for a given number of potential locations. In each variant, twoholes 340 are present, one large and one small. The base unit 100 hastwo pegs 140, also one large and one small. If the locations and sizesof the holes and pegs match (FIG. 13A) then the aerosol head interlockswith, and fits onto, the base unit (FIG. 13C). An advantage of thissystem is that the pegs and holes are visible, so that the user caneasily judge whether the aerosol head and base unit will fit together,i.e. are complementary. Nevertheless, if the user does attempt to use anincorrect aerosol head for the base unit, then the pegs do not match theholes (FIG. 13B). In this event, the pegs 140 hold the aerosol head 300slightly apart from the base unit 100 which prevents the respective keylock members from interlocking with each other. Thus the recognitionsystem provides both a strong visual cue for the correct combination ofthe aerosol head and base unit, and also a failsafe mechanism whichprevents incorrect combinations from being formed.

1. A dosing system for an inhalation device, comprising: (a) a fillingchamber for receiving a liquid to be aerosolized, the filling chamberhaving a first outer wall, a base and a first inner wall, the fillingchamber further having an outlet opening which is defined by the innerwall of the filling chamber, (b) a reservoir chamber for supplying theliquid to an aerosol generator positioned at a first end of the fillingchamber, wherein the reservoir chamber is operatively connected to theoutlet opening, and (c) a plunger which is mounted on a hinge and whichincludes an overflow chamber, said plunger being configured to beinserted into the filling chamber and said overflow chamber beingconfigured to receive at least a portion of the liquid from the fillingchamber when the plunger is inserted into the filling chamber, wherein afirst portion of the inner wall of the filling chamber proximate to thehinge is higher than a second portion of the inner wall of the fillingchamber distal from the hinge with respect to the first portion of theinner wall of the filling chamber so that when the filling chamber isfilled with liquid and the plunger is inserted into the filling chamberby pivoting it about the hinge, part of the liquid is displaced by theplunger over the lower side of the inner wall of the filling chamber andinto the reservoir chamber via the outlet opening, and some or all ofthe remaining liquid is displaced by the plunger from the fillingchamber into the overflow chamber.
 2. The dosing system of claim 1,further comprising a cap positioned at a second end the filling chamberopposite from the first end and configured to obstruct the outletopening at the second end to prevent the liquid from being supplieddirectly into the reservoir chamber.
 3. The dosing system of claim 1,wherein the plunger further comprises a second inner wall and a secondouter wall, and wherein at least part of the first inner wall and firstouter wall of the filling chamber and the second inner wall and secondouter wall of the plunger are curved.
 4. The dosing system of claim 1,further comprising a partition located within the outlet opening of thefilling chamber, wherein the partition extends into the reservoirchamber.
 5. The dosing system of claim 2 wherein the cap is formed as anextension of the partition.
 6. The dosing system of claim 1, wherein theoverflow chamber further comprises a cover which is configured to closethe top of the overflow chamber on a side adjacent to the hinge.
 7. Thedosing system of claim 1, wherein the plunger further comprises a lid.8. The dosing system of claim 7, further comprising an opening betweenthe lid and a top end of the overflow chamber, wherein the lid is fixed.9. The dosing system according of claim 7, wherein the overflow chamberand the lid are separately pivotable.
 10. The dosing system of claim 1,wherein the overflow chamber corresponds to the size and shape of thefilling chamber, so that the plunger occupies substantially the whole ofthe filling chamber when inserted into the filling chamber.
 11. Thedosing system of claim 1, wherein the filling chamber and the plungerare made from a rigid material.
 12. An inhalation device comprising thedosing system of claim
 1. 13. The inhalation device of claim 12, furthercomprising an aerosol head comprising the dosing system and a base unit,wherein the aerosol head and base unit are detachably connectible witheach other, and wherein the aerosol head and base unit havecomplementary male and female features which interlock to provide arecognition system.
 14. inhalation system of claim 13, wherein the baseunit comprises the male features and the aerosol head comprises thefemale features, wherein the male features comprise two pegs ofdifferent sizes and the female features comprise two holes sized tocorrespond with the different sizes of the two pegs, respectively.
 15. Amethod for dosing liquid to an inhalation device of claim 12, the methodcomprising supplying the liquid to be aerosolized to the fillingchamber, and inserting the plunger into the filling chamber so that afirst part of the liquid is displaced over the first portion of theinner wall of the filling chamber into the reservoir chamber and asecond part of liquid is displaced into the overflow chamber.
 16. Thedosing system of claim 9, wherein the overflow chamber and lid eachcomprise clip formations configured to attach the lid to the overflowchamber when the lid is closed.
 17. The dosing system of claim 1,wherein the filling chamber and the plunger are made from a rigidplastic.